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A rapid screening of hazard method (RASH) is presented for deriving relative potency estimates for hazardous substances. The method utilizes data from any available toxicological database such as the Registry of Toxic Effects of Chemical Substances (RTECS) or EPA's GENE-TOX database on genetic activity profiles. The method has been applied to derive relative potency values and permissible environmental concentrations for 278 chemicals. The derived values have been compared with recommendations of expert committees where possible, and substantial agreement is found.

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Many radiation-induced lethality experiments have been published for various mammalian species. From those studies a subset of studies reflecting useful biological and physical variables has been compiled into a database suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behavior within each experiment, etc. The data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Photon source energy, exposure geometry, and body weight considerations were used to select studies where the dose to hematopoietic tissue was approximately uniform. The database reflects 13 mammalian species ranging in size from mouse to cattle. Some 211 studies were compiled, but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to practical human exposures. Of the 105 studies, 70 were for various rodent species, and 35 were for non-rodent groups ranging from standard laboratory primates (body weight approximately 5 kg) to cattle (body weight approximately 375 kg). This paper considers seven different dose-response models which are tested for validity against those 105 studies. The dose-response models include: right-skewed extreme value, left-skewed extreme value, log-logistic, log-probit, logistic, probit, and Weibull models. In general, the log transformation models did not improve model performance and the extreme value models did not seem consistent with the preponderance of the data. Overall, the probit and the logistic models seemed preferable over the Weibull model.

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Many chemicals are of concern to human health, but only a few have epidemiologically derived risk estimates. About 45,000 chemicals are listed in RTECS, most of which have had some testing in subhuman models. RTECS entries range from cellular effects through organoleptic damage to lethality, with many pathological endpoints listed, including mutagenic changes, irritation, teratogenesis, cancer, mortality, etc. However, it is difficult to extend any biological test results to human risk assessments. If the results are extended, the degree of validity is highly uncertain. This paper describes a logical basis for using the entire complex spectrum of test results to evaluate the overall toxicological potency of a chemical to be assayed (i.e., an interviewing chemical) and describes how to derive tentative, permissible concentrations in air and water for any particular chemical for which no regulatory guidance exists. This approach has been tested for 16 reference chemicals discussed in NIOSH Criteria Documents, EPA-CAG reports, etc. The evaluations are uncomplicated, but occasionally it is difficult to match RTECS entries for two different chemicals. Difficult comparisons may require some familiarity with experimental design and the toxicological literature. One important product of this novel approach is that a distribution or array of potency values is obtained for any chemical evaluated. This distribution reflects many uncertainties stemming from low statistical power, experimental design, pharmacological processes, interspecies variability, dose rate, biological effect monitored, route of treatment, etc. The array of relative values for a particular chemical reflects many different biological and physical conditions. The distribution of the array helps to index a composite toxicological profile for many different biological effects resulting from numerous treatment protocols. To minimize the effect of extreme sensitivity of certain (perhaps novel) biological test models, possible errors in the RTECS data-base, and possible human pharmacological insensitivity to a particular chemical and/or a particular route of administration, we consider the interquartile range (i.e., the central 50%) of the array of relative potency values between two chemicals being compared as a practical measure of uncertainty. Thus, the range in response derived from variability in relative potency should be useful in addressing the range of response in man as estimated from extrapolations of test data.

This paper presents a new, general mathematical dose-response model which can use human, animal and cell culture data to predict the incidence of leukemia as a result of exposure to ionizing radiations. The model is based on simple considerations of fundamental biological processes of carcinogenic initiation, carcinogenic promotion and competing risk due to other toxic or disease reactions. The model can be used to predict the risk of leukemia for either human or animal populations which have been (or will be) treated with any radiation dose-time treatment protocol of interest. The model is both an extension and an outgrowth of earlier work done for the Oak Ridge dosimetry program in support activities for the Atomic Bomb Casualty Commission (formerly) and the Radiation Effects Research Foundation (currently).

We use a method of relative potency comparisons to rank the potential strength of 44 compounds being tested in rodent carcinogenicity bioassays. All of our previous hazard evaluations have been for human conditions where great numbers of simultaneous and serial exposures may act in combination to produce a neoplasm comprised of 2(20) to 2(30) cells commonly expected to derive from a single precancerous cell. For human exposures, we have always assumed an initiated target tissue containing at least one transformed but subcarcinogenic cell per organ. Thus, for man we have focused on empirical correspondences that may help to index the monoclonal growth of a particular cell lineage during cancer expansion. In contrast to humans, initiation of target tissues in animals subjected to National Toxicity Program (NTP) bioassays may not be a given condition, because of extensive precautions taken to minimize exposures to contaminates in food, water and cage environments. For this evaluation, we used categorical assignments of 'unlikely', 'possible' and 'probable' carcinogens adapted from NTP tests. Our rank ordering, of compounds according to maximum doses tested in male mice and male rats, is coded accordingly to the three outcomes taken from the NTP tests, but the magnitude of potency depend completely upon our particular method of comparing toxicological data. We have attempted to demonstrate that a relative potency based analysis of a diversity of toxicological data may be useful for rank ordering potentially hazardous compounds to be tested by the NTP and for range-finding of their effective test doses to be administered during chronic test protocols.